Timothy E. Lindley

Superoxide Is Involved in the Central Nervous System Activation and Sympathoexcitation of Myocardial Infarction-Induced Heart Failure

Abstract— Increased angiotensin II signaling in the brain has been shown to play a critical role in the excessive sympathoexcitation and development of heart failure (HF) after myocardial infarction (MI). We have recently demonstrated that reactive oxygen species mediate the actions of angiotensin II in the brain. In this study, we tested the hypothesis that increased redox signaling in central cardiovascular control regions is a key mechanism in the neurocardiovascular dysregulation that follows MI. Ligation of the left coronary artery induced a large MI and subsequent HF in adult C57BL/6 mice, as demonstrated by cardiac hypertrophy, hydrothorax, and ascites. Immunohistochemical analysis of Fos, a marker of neuronal activation, revealed a significant increase in the number of Fos-positive neurons in the paraventricular nucleus and supraoptic nucleus at 2 and 4 weeks after MI compared with sham mice. Intracerebroventricular injection of an adenoviral vector encoding superoxide dismutase (Ad-Cu/ZnSOD) caused a significant decrease in the number of Fos-positive neurons in the paraventricular nucleus and supraoptic nucleus at 2 weeks after MI compared with mice receiving either saline or a control vector (Ad-LacZ). There was also a diminished role of sympathetic drive in post-MI mice treated centrally with Ad-Cu/ZnSOD, as demonstrated by significantly attenuated falls in heart rate and mean arterial pressure to the ganglionic blocker hexamethonium and decreased urinary norepinephrine levels in these mice compared with Ad-LacZ–treated MI mice. These results suggest that superoxide plays a key role in the central activation and sympathetic hyperactivity after MI in mice and that oxygen radicals in the brain may be important new targets for therapeutic treatment of heart failure.

Complications associated with recombinant human bone morphogenetic protein use in pediatric craniocervical arthrodesis: Clinical article

OBJECT Management of pediatric occipitocervical instability remains especially challenging. The off-label use of recombinant human bone morphogenetic protein (rhBMP)-2 for spinal fusion has increased with a well-documented increase in fusion rate in many case series. Unfortunately, recent reports have documented complications associated with rhBMP use in adult spinal fusions. Complications associated with the use of rhBMP in pediatric spinal surgery is less well understood. In this study the authors report on the fusion rate and complications associated with rhBMP in pediatric occipitocervical arthrodesis. METHODS The authors reviewed the medical records of those patients 18 years old and younger who underwent dorsal occipitocervical fusion from January 2004 to December 2007 at the University of Iowa Hospitals and Clinics. Forty-eight patients were identified who received rhBMP-augmented fusion. The clinical outcome and complications of these fusions were analyzed. RESULTS All 48 patients had fusion confirmed on lateral radiographs within 4-14 months with an average fusion time of 6.7 months. There were 6 complications, 5 of which included seroma formation. Two of 5 patients who developed postoperative seroma presented with symptoms suggesting brainstem compression and obstructive hydrocephalus requiring emergency reoperation. One patient developed heterotopic bone formation causing cervicomedullary compression requiring reoperation. CONCLUSIONS The use of rhBMP to augment autograft in occipitocervical fusion allows for a high rate of successful arthrodesis, but is associated with potentially life-threatening complications in pediatric patients.

Loss of Acid Sensing Ion Channel-1a and Bicarbonate Administration Attenuate the Severity of Traumatic Brain Injury

Traumatic brain injury (TBI) is a common cause of morbidity and mortality in people of all ages. Following the acute mechanical insult, TBI evolves over the ensuing minutes and days. Understanding the secondary factors that contribute to TBI might suggest therapeutic strategies to reduce the long-term consequences of brain trauma. To assess secondary factors that contribute to TBI, we studied a lateral fluid percussion injury (FPI) model in mice. Following FPI, the brain cortex became acidic, consistent with data from humans following brain trauma. Administering HCO3 − after FPI prevented the acidosis and reduced the extent of neurodegeneration. Because acidosis can activate acid sensing ion channels (ASICs), we also studied ASIC1a−/− mice and found reduced neurodegeneration after FPI. Both HCO3 − administration and loss of ASIC1a also reduced functional deficits caused by FPI. These results suggest that FPI induces cerebral acidosis that activates ASIC channels and contributes to secondary injury in TBI. They also suggest a therapeutic strategy to attenuate the adverse consequences of TBI.

A “neurosurgical crisis” of sickle cell disease

The occurrence of spontaneous acute epidural hematomas is rare in patients with sickle cell disease. The authors report the case of a patient with sickle cell anemia who presented with a sickle cell crisis that was complicated by the development of multiple acute epidural and subgaleal hematomas requiring surgical evacuation. Possible underlying mechanisms are discussed. Although rare, clinicians should be aware of this phenomenon as part of a spectrum of neurological complications in these patients.

Effect of steerable cage placement during minimally invasive transforaminal lumbar interbody fusion on lumbar lordosis.

Minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) is commonly used for the treatment of a variety of degenerative spine disorders. Recently, steerable interbody cages have been developed which potentially allow for greater restoration of lumbar lordosis. Here we describe a technique and radiographic results following minimally invasive placement of steerable cages through a bilateral approach. A retrospective review was conducted of the charts and radiographs of 15 consecutive patients who underwent 19 levels of bilateral MIS-TLIF with the placement of steerable cages. These were compared to 10 patients who underwent 16 levels of unilateral MIS-TLIF with the placement of bullet cages. The average age, body mass index, distribution of the levels operated and follow-up were similar in both groups. The average height of the steerable cage placed was 10.9 mm compared to 8.5mm for bullet cages. The preoperative focal Cobbs angle per level was similar between both groups with a mean of -5.3 degrees for the steerable cage group and -4.8 degrees for the bullet cage group. There was a significant improvement in postoperative Cobbs angle after placement of a steerable cage with a mean of -13.7 (p<0.01) and this persisted at the last follow-up with -13 degrees (p<0.01). There was no significant change in Cobbs angle after bullet cage placement with -5.7 degrees postoperatively and a return to the baseline preoperative Cobbs angle of -4.8 at the last follow-up. Steerable cage placement for MIS-TLIF improves focal lordosis compared to bullet cage placement.

Intracranial glioblastoma with drop metastases to the spine after stereotactic biopsy

BACKGROUND Glioblastoma (GBM) is the most common primary intracranial tumor, but metastases are rarely reported. Previous reports have documented the occurrence of drop metastases to the spine. However, few of these reports have demonstrated the occurrence of spinal metastases after biopsy with stable intracranial disease. Here we present such a case. CASE DESCRIPTION We present a case of GBM metastatic to the spinal cord after a stereotactic biopsy with stable intracranial disease. To our knowledge, this occurrence has only been reported in one previous case. CONCLUSION We propose that traversing the lateral ventricle at the time of biopsy contributed to cerebrospinal fluid seeding with tumor cells and subsequent development of spinal disease.

Successful Treatment of a Three-Column Thoracic Extension Injury with Recumbency

We report a unique instance of a 66-year-old male patient with an unstable three-column thoracic extension injury at the level of T4/5 who was treated with recumbency and bracing without surgery. A posterior long segment fixation was attempted three times on two separate occasions over the course of a week with failure due to difficulty in ventilating the patient during prone positioning, cardiopulmonary arrest, and hemodynamic instability during prone positioning for surgery. The decision then was to treat this fracture with recumbency. He was fitted with a thoracolumbosacral orthosis (TLSO), and was kept on bed rest for eight weeks. The patient’s activity was advanced to head of bed for 45 degrees for four weeks and then to 90 degrees for four other weeks. At his 16th week visit, the patient was asymptomatic, and a computer tomography (CT) scan and magnetic resonance imaging (MRI) of the thoracic spine demonstrated evidence of osteophyte bridging and restoration of normal alignment. Three-column thoracic extension injuries can be successfully treated with recumbency in poor surgical candidates.

Acute Presentation of Lumbar Spinal Schwannoma Due to Torsion: A Case Report.

Although schwannomas are common spinal tumors with insidious presentations, acute neurological deterioration is an extremely rare manifestation that can occur in the setting of tumor torsion and infarction. The present case reports an unusual presentation of a spinal schwannoma that underwent torsion and infarction. A 65-year-old male presented initially with acute radicular pain progressing to cauda equina syndrome and confusion. MRI of the lumbar spine revealed an intradural extramedullary lesion at the level of L1/L2 measuring 1.1x0.9 cm. Intraoperatively, a reddish mass was seen caudally twisted around itself. Gross total resection was achieved with a final diagnosis of schwannoma with areas of infarction. At his six week follow up clinical visit, the patient was asymptomatic and his neurological exam was normal. The neurosurgeon should be aware of such atypical radiographic and clinical presentation amongst the spectrum of clinical manifestation of these nerve sheath tumors.